VERNIER R L, PAPERMASTER B W, GOOD R A
J Exp Med. 1959 Jan 1;109(1):115-26. doi: 10.1084/jem.109.1.115.
Experimental renal disease was produced in young rats by daily subcutaneous injections of 6-dimethylamino purine, 3-amino-d-ribose (aminonucleoside). The physiologic, biochemical, and light microscopic changes were similar to those observed in human nephrosis. Electron microscopy of the glomeruli from animals which received seven or more daily injections of aminonucleoside revealed characteristic abnormalities of the epithelial cells of the glomerular capillaries. These changes consisted of swelling, coalescence, and eventual obliteration of the epithelial cell foot processes and an increase in the number and the size of epithelial cytoplasmic vacuoles. The serial development of the ultramicroscopic pathologic changes in the epithelial cells, as observed by study of animals through the course of the disease, indicated that the smudging of the foot processes occurred at the time of onset of severe proteinuria. Further changes, consisting of hypercellularity due primarily to an increase in the number of endothelial cells and an increase in the amount of basement membrane-like material, were regularly observed by the 12th day after injections were begun. These abnormalities were correlated with the development of uremia in the later stages of the disease process. The distal and proximal renal tubules were abnormal by the 7th day after injections were begun, and showed localized swelling between the cristae of the mitochondria and a decrease in over-all cytoplasmic density, described as hydropic change. Electron microscopy of glomeruli from animals which had partially recovered from aminonucleoside nephrosis revealed areas of normal epithelial cell morphology. This observation was interpreted as evidence of partial reversal of the ultramicroscopic changes in the recovery phase of the disease. These observations of the fine structure of pathologically altered glomeruli and tubules in aminonucleoside nephrosis are similar to our findings in human nephrosis as revealed by electron microscopy of serial renal biopsies.
通过每日皮下注射6 - 二甲基氨基嘌呤、3 - 氨基 - D - 核糖（氨基核苷）在幼鼠中诱发实验性肾病。其生理、生化及光镜下变化与人类肾病中观察到的相似。对每日接受七次或更多次氨基核苷注射的动物的肾小球进行电子显微镜检查，发现肾小球毛细血管上皮细胞有特征性异常。这些变化包括上皮细胞足突肿胀、融合，最终消失，以及上皮细胞质空泡数量和大小增加。通过对患病过程中的动物进行研究观察到，上皮细胞超微病理变化的连续发展表明，足突模糊出现在严重蛋白尿发作之时。进一步的变化，主要是由于内皮细胞数量增加和基底膜样物质增多导致的细胞增多，在开始注射后的第12天经常可以观察到。这些异常与疾病后期尿毒症的发展相关。在开始注射后的第7天，远端和近端肾小管出现异常，表现为线粒体嵴之间局部肿胀以及整体细胞质密度降低，称为水样变性。对已从氨基核苷肾病部分恢复的动物的肾小球进行电子显微镜检查，发现有上皮细胞形态正常的区域。这一观察结果被解释为疾病恢复阶段超微变化部分逆转的证据。这些对氨基核苷肾病中病理改变的肾小球和肾小管精细结构的观察结果与我们通过对系列肾活检进行电子显微镜检查在人类肾病中的发现相似。
